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P05126 (KPCB_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein kinase C beta type

Short name=PKC-B
Short name=PKC-beta
EC=2.7.11.13
Gene names
Name:PRKCB
Synonyms:PRKCB1
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length671 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shcof SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. May participate in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Binds 3 calcium ions per subunit. The ions are bound to the C2 domain By similarity.

Enzyme regulation

Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615) By similarity.

Subunit structure

Interacts with PDK1. Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Membrane; Peripheral membrane protein By similarity.

Post-translational modification

Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Autophosphorylation on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity. Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 C2 domain.

Contains 2 phorbol-ester/DAG-type zinc fingers.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processAdaptive immunity
Apoptosis
Immunity
Transcription
Transcription regulation
   Cellular componentCytoplasm
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   DomainRepeat
Zinc-finger
   LigandATP-binding
Calcium
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionChromatin regulator
Kinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell activation

Inferred from sequence or structural similarity. Source: UniProtKB

B cell receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

calcium ion transport

Inferred from electronic annotation. Source: Ensembl

cellular calcium ion homeostasis

Inferred from electronic annotation. Source: Ensembl

cellular response to carbohydrate stimulus

Inferred from electronic annotation. Source: Ensembl

histone H3-T6 phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

negative regulation of glucose transport

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of B cell receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

androgen receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

calcium channel regulator activity

Inferred from electronic annotation. Source: Ensembl

chromatin binding

Inferred from sequence or structural similarity. Source: UniProtKB

histone binding

Inferred from sequence or structural similarity. Source: UniProtKB

histone kinase activity (H3-T6 specific)

Inferred from sequence or structural similarity. Source: UniProtKB

ligand-dependent nuclear receptor transcription coactivator activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase C activity

Inferred from electronic annotation. Source: UniProtKB-EC

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Beta-I (identifier: P05126-1)

Also known as: PRKCB1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Beta-II (identifier: P05126-2)

Also known as: PRKCB2;

The sequence of this isoform differs from the canonical sequence as follows:
     622-671: RDKRDTSNFD...YTNPEFVINV → CGRNAENFDR...SEFLKPEVKS

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 671670Protein kinase C beta type
PRO_0000055683

Regions

Domain173 – 26088C2
Domain342 – 600259Protein kinase
Domain601 – 66969AGC-kinase C-terminal
Zinc finger36 – 8651Phorbol-ester/DAG-type 1
Zinc finger101 – 15151Phorbol-ester/DAG-type 2
Nucleotide binding348 – 3569ATP By similarity

Sites

Active site4661Proton acceptor By similarity
Metal binding1861Calcium 1; via carbonyl oxygen By similarity
Metal binding1871Calcium 1 By similarity
Metal binding1871Calcium 2 By similarity
Metal binding1931Calcium 2 By similarity
Metal binding2461Calcium 1 By similarity
Metal binding2461Calcium 2 By similarity
Metal binding2471Calcium 2; via carbonyl oxygen By similarity
Metal binding2481Calcium 1 By similarity
Metal binding2481Calcium 2 By similarity
Metal binding2481Calcium 3 By similarity
Metal binding2511Calcium 3 By similarity
Metal binding2521Calcium 3; via carbonyl oxygen By similarity
Metal binding2541Calcium 1 By similarity
Metal binding2541Calcium 3 By similarity
Binding site3711ATP By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue161Phosphoserine; by autocatalysis Potential
Modified residue171Phosphothreonine; by autocatalysis Potential
Modified residue2501Phosphothreonine; by autocatalysis By similarity
Modified residue3241Phosphothreonine; by autocatalysis Potential
Modified residue5001Phosphothreonine; by PDPK1 By similarity
Modified residue5041Phosphothreonine By similarity
Modified residue6351Phosphothreonine; by autocatalysis By similarity
Modified residue6421Phosphothreonine; by autocatalysis By similarity
Modified residue6611Phosphoserine; by autocatalysis By similarity
Modified residue6621Phosphotyrosine; by SYK By similarity

Natural variations

Alternative sequence622 – 67150RDKRD…FVINV → CGRNAENFDRFFTRHPPVLT PPDQEVIRNIDQSEFEGFSF VNSEFLKPEVKS in isoform Beta-II.
VSP_039222

Experimental info

Sequence conflict5761M → I in AAA30703. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform Beta-I (PRKCB1) [UniParc].

Last modified May 18, 2010. Version 4.
Checksum: 1F31D6A9D3C4C61F

FASTA67176,790
        10         20         30         40         50         60 
MADPAAGPPP SEGEESTVRF ARKGALRQKN VHEVKNHKFT ARFFKQPTFC SHCTDFIWGF 

        70         80         90        100        110        120 
GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPASDDPRS KHKFKIHTYS SPTFCDHCGS 

       130        140        150        160        170        180 
LLYGLIHQGM KCDTCMMNVH KRCVMNVPSL CGTDHTERRG RIYIQAHIER EVLIVVVRDA 

       190        200        210        220        230        240 
KNLVPMDPNG LSDPYVKLKL IPDPKSESKQ KTKTIKCSLN PEWNETFRFQ LKESDKDRRL 

       250        260        270        280        290        300 
SVEIWDWDLT SRNDFMGSLS FGISELQKAG VDGWFKLLSQ EEGEYFNVPV PPEGSEGNEE 

       310        320        330        340        350        360 
LRQKFERAKI GPGPKTPEEK TTNTISKFDN NGNRDRMKLT DFNFLMVLGK GSFGKVMLSE 

       370        380        390        400        410        420 
RKGTDELYAV KILKKDVVIQ DDDVECTMVE KRVLALPGKP PFLTQLHSCF QTMDRLYFVM 

       430        440        450        460        470        480 
EYVNGGDLMY HIQQVGRFKE PHAVFYAAEI AIGLFFLQSK GIIYRDLKLD NVMLDSEGHI 

       490        500        510        520        530        540 
KIADFGMCKE NIWDGVTTKT FCGTPDYIAP EIIAYQPYGK SVDWWAFGVL LYEMLAGQAP 

       550        560        570        580        590        600 
FEGEDEDELF QSIMEHNVAY PKSMSKEAVA ICKGLMTKHP GKRLGCGPEG ERDIKEHAFF 

       610        620        630        640        650        660 
RYIDWEKLER KEIQPPYKPK ARDKRDTSNF DKEFTRQPVE LTPTDKLFIM NLDQNEFAGF 

       670 
SYTNPEFVIN V 

« Hide

Isoform Beta-II (PRKCB2) [UniParc].

Checksum: 61711D08707B005B
Show »

FASTA67376,933

References

« Hide 'large scale' references
[1]"Multiple, distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways."
Coussens L., Parker P.J., Rhee L., Yang-Feng T.L., Chen E., Waterfield M.D., Francke U., Ullrich A.
Science 233:859-866(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-II).
[2]NIH - Mammalian Gene Collection (MGC) project
Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-I).
Strain: Hereford.
Tissue: Fetal pons.
[3]"The molecular heterogeneity of protein kinase C and its implications for cellular regulation."
Nishizuka Y.
Nature 334:661-665(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M13974 mRNA. Translation: AAA30703.1.
BC140620 mRNA. Translation: AAI40621.1.
PIRKIBOC2. A24664.
RefSeqNP_777012.1. NM_174587.1.
XP_005224747.1. XM_005224690.1.
UniGeneBt.5435.

3D structure databases

ProteinModelPortalP05126.
SMRP05126. Positions 37-288, 339-668.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid159587. 1 interaction.
STRING9913.ENSBTAP00000027870.

Proteomic databases

PRIDEP05126.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSBTAT00000027870; ENSBTAP00000027870; ENSBTAG00000020921. [P05126-2]
ENSBTAT00000042942; ENSBTAP00000040548; ENSBTAG00000020921. [P05126-1]
GeneID282325.
KEGGbta:282325.

Organism-specific databases

CTD5579.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117339.
HOGENOMHOG000233022.
HOVERGENHBG108317.
InParanoidP05126.
KOK02677.
OMAQAHIDRE.
OrthoDBEOG77M8QM.
TreeFamTF351133.

Enzyme and pathway databases

BRENDA2.7.11.13. 908.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR014375. Protein_kinase_C_a/b/g.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000550. PKC_alpha. 1 hit.
PRINTSPR00360. C2DOMAIN.
PR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS50004. C2. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 2 hits.
PS50081. ZF_DAG_PE_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio20806122.

Entry information

Entry nameKPCB_BOVIN
AccessionPrimary (citable) accession number: P05126
Secondary accession number(s): A5D7N0
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 149 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families